The Johns Hopkins SPORE program for lung cancer, functioning as a major element of the Johns Hopkins Comprehensive Cancer Center, would represent a multidisciplinary and highly collaborative translational research effort to develop new strategies for early detection, prevention and treatment of lung cancer. Included will be an emphasis upon enhancing entry of new investigators into careers in lung cancer research -- and encouragement of novel research approaches through funding of pilot projects. The work scope of the SPORE addresses most of the research imperatives defined at the 1991 Annapolis Lung Cancer Workshop. A major emphasis is devoted to defining, at a molecular level, the earliest steps in lung cancer evolution. The goal is to develop markers which will be tested for efficacy in predicting and/or detecting early lung cancer and which will serve as new tools for guiding prevention and early treatment strategies. Unique tissue acquisition efforts of a Core Tissue Resource will allow isolated fresh and cultured human bronchial epithelium to be studied for timing of genetic (allelic losses, gene mutations) and epigenetic (changes in DNA methylation, neuroendocrine differentiation, signal transduction events, monoclonal antibody recognition) abnormalities in lung cancer progression. The research will include studies of unique patient cohorts for lung cancer risk, including uranium miners and individuals at genetic risk, and studies of unique rodent models for lung cancer induction. Novel treatment strategies for lung cancer, based on molecular targets defined in the laboratory, will be evaluated in focused clinical trials. Included will be molecular biology and biochemical assays to predict and monitor responses. Novel polyamine analogues active, through a newly defined gene induction event, against non-small cell lung cancer (NSCLC) will receive an initial clinical trial. The observation that retinoids can block a tumor progression step for small cell lung cancer cells, in a laboratory model, will be translated into a clinical trial to prevent, or delay, drug resistance for this cancer. In summary, this SPORE program represents an exciting collaborative opportunity for basic and clinical investigators to translate understanding of fundamental biology into new means to prevent, detect and treat lung cancer.